Ovarian cancer of epithelial origin accounts for more than half of the deaths caused by gynecological malignancy. More than two-thirds of patients with ovarian cancer fail to show symptoms until late in the development of disease and the five-year survival rate is less than 20 percent. In contrast, the five-year survival rate is greater than 90 percent if the cancer is detected before it has spread from the ovaries. Thus, methods for early detection and/or prevention of the development of ovarian cancer are of paramount importance to improve the prognosis and overall survival of ovarian patients. Secreted and membrane-associated proteins can be an enriched resource for potential tumor markers for tumor diagnosis and targets for cancer treatment. Studies by us, and others have identified several secreted serine proteases from the serine hydrolase superfamily, which either have been established or are being developed as biomarkers for ovarian and other cancers. In this proposal, we will perform (1) expression profiling of membrane-associated polyribosome RNA for over-expressed transcripts encoding secreted and membrane-bound proteins in ovarian cancer by cDNA microarray analysis and subtracted cDNA library screening; and (2) a dynamic expression and activity profiling of serine hydrolases in ovarian cancer by an active-site directed probe. This study is based on the hypothesis that a systematic comparison of membrane-associated polyribosome RNA transcripts and serine hydrolase family proteins between normal ovarian epithelial cells and tumor cells by high-throughput screenings will reveal potential markers for ovarian cancer. The clinical relevance of the chosen potential markers will be evaluated in a large number of tumor samples. The identified markers will be studied in the future for their physiological functions, possible involvement in the etiology of ovarian cancer, and potential as diagnostic tools for ovarian cancer and new drug development. It is expected that this genome-wide study will identify potential markers for early detection and intervention of ovarian cancer, and thereby improve the overall survival rate of patients with ovarian cancer.